The overall objectives of this BETRNet Translational Research Center (TRC-F) are: 1) to conduct a rigorous, integrated spectrum of transdisciplinary human research in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) 2) to increase the biological understanding of key observations made by our clinical researchers (familial aggregation of BE and EAC, restitution of squamous mucosa after ablation); 3) to translate knowledge derived from genetic and physiologic research to solving clinical dilemmas in detection, prognosis, and therapy of BE in order to prevent EAC and improve the outcomes of EAC;4) to foster a transdisciplinary and translational research culture and to effectively expand and enhance scientific research focused on BE and EAC; 5) to evaluate research and transdisciplinary programs and to continuously Improve research, productivity and enhance translational implementation. These objectives build and synergize on existing multi-institutional collaborative networks and the considerable clinical, basic science, and translational expertise available at our institutions, focusing on improving the outcomes of patients with BE and EAC. The overarching organization framework for this TRCF proposal is 1) to focus research on understanding the genetic susceptibility, genomic and epigenetic changes that influence the development of BE and EAC; 2) to explore the physiologic, transcriptional, and epigenetic factors that lead to durable ablation of BE; and 3) to translate discoveries into applications that improve familial screening, effective detection, molecular prognostication, and durable ablation of BE.